As of September, 1997 the complete genome sequences of 12 microbes had been obtained representing all three domains of cellular life. The annotation of genes corresponding to ORFs relies heavily on sequence data from the best studied microbes (e.g. E. coli, B. subtilis, and S. cerevisiae) or from heterologous sequences that are cloned into E. coli. Yet even with a great deal of extrapolation, the percentage of genes with an "ascribed function" ranges from only 44% to 69%. The most pressing current need is to develop efficient, cost-effective, and reliable technologies for determining the function of genes (functional genomics). Technologies developed thus far have emphasized molecular approaches. The goal of this project is to develop a complementary cellular approach to this problem consisting of an instrument using inexpensive disposable testing panels that will allow biologists to assay cell lines directly and simultaneously for thousands of phenotypes. In Phase I we will focus on developing testing panels for E. coli. In Phase II we will expand the work and include an equal effort on S. cerevisiae. These procaryotic and eucaryotic microorganisms will serve as genomic models for other types of cells including mammalian cells. PROPOSED COMMERCIAL APPLICATION: Genomic analysis is very important and receiving a substantial portion of the research budget in government and university research laboratories funded by NIH and DOE, and in genomics companies, biotech companies, and pharmaceutical companies. We therefore anticipate a significant market for the testing system that would be developed under this proposal.